1.Relationship between toxicity of baicalin-metal complexes on human hepatoma SMMC-7721 cells and interaction of baicalin-metal complexes with hepatoma cell DNA
Ming GUO ; Zhouiing WU ; Xiaoyan GAO
Chinese Journal of Pharmacology and Toxicology 2014;(4):536-549
OBJECTlVE To investigate the correIation between baicaIin metaI(Ni2+,Co2+,Cu2+) compIexes(BmC)with their anti-tumor activity and the abiIity of BmC to bind to hepatoma ceII DNA. METHODS The cheIating Iigand method was used to synthesize BmC,and the composition and struc-ture of BmC were characterized. mTT,PI staining method and AnnexinⅤ-FITC doubIe staining method were used to anaIyze the effect of BmC on SmmC-7721 ceII proIiferation,cycIe and apoptosis,and to expIore their cytotoxic effect on SmmC-7721 ceIIs in combination with morphoIogy. With DNA extracted from hepatoma ceIIs as a target,cycIic voItammetry and AC impedance were used to study the interaction of BmC with DNA. The interaction mechanism between BmC and DNA was expIored. RESULTS Three new types of BmS were successfuIIy prepared. The moIecuIar formuIas of compIexes were Na2 Ni(C21 H16 O11 )2·10H2 O,Na2 Co(C21 H16 O11 )2·8H2 O,and Na2 Cu(C21 H16 O11 )2·8H2 O,respec-tiveIy. CeII proIiferation and morphoIogy detection reveaIed that BmC 6.25-100 mg·L-1 treatment for 24, 48 and 72 h couId inhibit SmmC-7721 ceII survivaI. BmC cytotoxicity was Iisted as foIIows:baicaIin-cop-per( BC-Cu)﹥ baicaIin-cobaIt( BC-Co)﹥ baicaIin-nickeI( BC-Ni)﹥ baicaIin( BC),in a concentration-dependent manner(P﹤0.01)and time-dependent manner(P﹤0.01). According to the resuIts of ceII cycIe and apoptosis detection,BmC retarded the growth of ceIIs from G0 / G1 phase into S phase or G2 / m phase whiIe inducing apoptosis of SmmC-7721 ceIIs. The resuIts of eIectrochemicaI anaIysis showed that BmC and hepatoma SmmC-7721 ceII DNA formed a non-eIectroactive supermoIecuIar compound through the mixed-mode of eIectrostatic interaction and insertion effect. The binding parameters were obtained:the binding number m = 2,the binding constant βBC = 2.77 ×106 L·moI-1 ,βBC-Ni = 5.46 ×106 L·moI-1 ,βBC-Co =7.74×106 L·moI-1 ,and βBC-Cu =1.21×107 L·moI-1 . The abiIity of BmC to bind to DNA was signifi-cantIy enhanced by BC compIexes with metaI ions,and their abiIity was Iisted as foIIows:BC-Cu﹥BC-Co﹥BC-Ni﹥BC. CONCLUSlON BmC shows cytotoxicity by bIocking the ceII cycIe,inhibiting ceII proIiferation and motivaing apoptosis. The abiIity of BmC to bind to DNA is consistent with its cytotoxicity. BmC,after binding to ceII DNA,wiII bIock DNA repIication,inhibit ceII proIiferation,Iead to ceII apoptosis,and exhibit anti-tumor activity.
2.Analysis of 30 Cases of Continuous Positive Airway Pressure Curing Overlap Syndrome.
Zhiqiang GUO ; Qiusheng CHEN ; Yuan-Ming GAO ;
Journal of Medical Research 2006;0(10):-
Objective To study the validity of continuous positive airway pressure(CPAP)curing overlap syndrome.Methods Comparisons were made in the respiratory disturbance index(RDI)the longest apnea time the longest hypopnea time etc between before and after-treatment.Results The respiratory disturbance index(RDI)、the longest apnea time、the longest hypopnea time were signifi- candy different(P<0.05).Conclusion Continuous positive airway pressure is an effective method to treat overlap syndrome.
3.Association of subclinical hypothyroidism with dyslipidemia and non-alcoholic fatty liver
Lingding XIE ; Yan-Ming GAO ; Gui-Zhi LU ; Qiu-Ming JIANG ; Xiao-Hui GUO ; Yan GAO
Chinese Journal of Endocrinology and Metabolism 2000;0(06):-
Objective To investigate the prevalence of subclinical hypothyroidism and its relation to serum total cholesterol (TC),triglyceride (TG) levels and non-alcoholic fatty liver.Methods Serum levels of TC,TG, TSH,TT_3 and TT_4 were determined in 1 602 subjects which were divided into groups by sex and age (20-39,40- 59 and≥60 years).Fatty liver was diagnosed by type B ultrasonography.Restults ( 1 ) Prevalence of subclinical hypothyroidism was 6.6% in this population.(2) The mean levels of serum TC and TG in subclinical hypothyroidism group and normal group showed no significant difference ( both P>0.05 ).(3) On the whole,the prevalences of subclinical hypothyroidism in hypercholesterolemia group and normal cholesterolemia group showed significant difference (P<0.01 ).(4) In the three age groups of male and few.ale examinees,the prevalences of subclinical hypothyroidism in hypercholesterulemla group and normal cholesterolemia group showed no significant difference ( all P>0.05 ).In the multiple regression analysis,TSH level was not related with raised TC level.(5) In the three age groups of male,there was no significant difference between the prevalences of subclinical hypothyroidism in hypertriglyceridemla group and normal triglyceridemia group ( all P>0.05 ).In female,expect for the elderly group (>60 years old ),the prevalence of subclinical hypothyroidism was higher in hypertriglyceridemia group than that in normal triglyceridemia.However,in the multiple regression analysis, increased TSH level was positively associated with increased serum TG level ( OR = 1.072,P=0.013 and OR = 1.102,P = 0.03 ).(6) The prevalence of subclinical hypothyroidism in non-alcobolic fatty liver group and normal group showed no significant difference ( P>0.05 ).In the multiple regression analysis,TSH level was not the independent risk factor of non-alcoholic fatty liver (P>0.05 ).Conclusion Subclinical hypothyroidism is not asseciated with serum TC level but positively associated with serum TG level.Subclinical hypothyroidism does not apparently increase the prevalence of non-alcoholic fatty liver.
4.Synthesis and anti-tumor activity of baicalin-metal complex.
Ming GUO ; Zhouling WU ; Chunge WANG ; Xiaoyan GAO
Acta Pharmaceutica Sinica 2014;49(3):337-45
Chelating ligand method has been used to synthesize baicalin-metal (Ni2+, Co2+, Cu2+) complexes (BMC). The composition and structure of BMC were characterized by the element analysis, ultraviolet spectrum (UV), infrared spectrum (IR), mass (MS) and thermal gravitational analysis (TGA). MTT was used to analyze the effects of BMC on SMMC-7721 cell proliferation. PI staining method and Annexin-V/FITC double staining method were used to analyze the effects of BMC on the cell cycle and apoptosis of SMMC-7721 cell. Fluorescence quantitative RT-PCR was used to analyze the expression of BMC on Bcl-2 gene and Bax mRNA, flow cytometry was used to analyze BMC on the expression of Bcl-2 protein and Bax protein. The antineoplastic activity and mechanism of action of BMC was explored comprehensively. The results showed that three new kinds of BMC (molar ratio of 2 : 1) were successfully prepared, the complexes molecular formula are: Na2Ni(C21H16O11)2 x 10H2O, Na2Co(C21H16O11)2 x 8H2O and Na2Cu(C21H16O11)2 x 8H2O. According to the results of cell cycle and apoptosis detection, BMC stopped cells at G0/G1 phase to S phase and G2/M phase. Gene and protein detection showed that under the given concentration and time, BMC can downregulate the expression of Bcl-2 gene in SMMC-7721 cells, and significantly decrease the expression of Bcl-2 protein, at the same time, with the increase of expression of Bax gene, the Bax protein's expression increased significantly. Which indicates that BMC restrain cell proliferation and cell apoptosis by stopping cell cycle, reducing the expression of Bcl-2 and increasing that of Bax; The anti-tumor activities of three kinds of complexes were: baicalin-copper (BC-Cu) > baicalin-cobalt (BC-Co) > baicalin-nickel (BC-Ni) > baicalin (BC), showing the dose-response relationship.
5.Association of serum angiopoietin-1 and angiopoietin-2 with ST-segment resolution in acute ;myocardial infarction patients treated with primary percutaneous coronary intervention
Shaomin CHEN ; Ming CUI ; Lijun GUO ; Wei GAO
Chinese Journal of Interventional Cardiology 2014;(4):246-250
Objective To investigate the association of serum angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) with myocardial reperfusion in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods A total of 103 consecutive STEMI patients who received primary PCI were enrolled in this study. The patients were divided into two groups according to ST-segment resolution (STR) at 2 h after PCI:STR ≥ 50%group (n=69) and STR<50%group (n=34). Serum concentrations of Ang-1, Ang-2 and Ang-2 to Ang-1 ratios (Ang-2/Ang-1) before and immediately after PCI, 2 h, 6 h, 24 h after PCI were compared. Predictors of poor STR were identiifed by multivariable logistic regression analysis. Results The patients with STR≥50%had significant higher serum Ang-1 levels (P < 0.05) and lower Ang-2/Ang-1 ratios (P < 0.01) from before PCI to 6 h after PCI than those with STR < 50%;Ang-1 and Ang-2/Ang-1 at 24 h after PCI, and Ang-2 at all time points were not signiifcantly different between the two groups (P>0.05). In multivariable logistic regression analysis, Ang-2/Ang-1 before PCI was independently associated with STR < 50%;Other independent predictors were pain to balloon time, infarct related artery (LAD), and TIMI flow grade<Ⅲafter PCI. Conclusions Higher Ang-2/Ang-1 is an independent predictor of poor myocardial reperfusion in STEMI patients after PCI.
6.The effect of scan duration on ALFF of resting-state fMRI
Hui DING ; Junjun LI ; Lei GAO ; Jianxin GUO ; Ming ZHANG
Journal of Practical Radiology 2014;(12):2061-2064
Objective To examine the reliability and similarity of amplitude of low-frequency fluctuation (ALFF)for different scan duration.Methods 10 min 10 s resting state fMRI data acquired from 13 healthy volunteers separately were divided into 10 pieces of the same length.The reliability and similarity of ALFF were assessed for each scan length (1-10 min).Results Spatial maps of ALFF steadily appeared in each time period (1-10 min);but during the time evolution,both spatial distribution and extent of ALFF increased gradually.At only one minute,there were detectable statistical differences within the group.When the time ran-ging from 5 to 10 min,relatively stable ALFF results in the group achieved.Conclusion ALFF is a relatively stable index,it can be easily affected by scan duration.In the case of 1-5 min,it should be carefully analyzed and interpretated particularly.
7.Detection of myocardial ischemia of hypertrophic cardiomyopathy with gated ~(99)Tc~m-MIBI myocardial perfusion imaging
Peng, JIA ; Wan-hua, GUO ; Ming-hua, DU ; Ling, GAO
Chinese Journal of Nuclear Medicine 2010;30(1):28-31
Objective To evaluate the value of gated ~(99)Tc~m-methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging in detection of myocardial ischemia in hypertrophic cardiomyopathy.Methods Sixty-nine patients with clinically proven hypertrophic cardiomyopathy were divided into 2 groups using coronary angiogram as "gold standard":positive group(n=19,narrowing≥50%) and negative group (n=50,narrowing<50%).Gated ~(99)Tc~m-MIBI myocardial perfusion imaging was performed and positive in all 69 patients (41 males,28 females,aged 35-75 years).Comparative analysis between the two groups was carried out using t-test.Results In the positive group,reversible and irreversible perfusion defects were detected in 9 and 10 patients,respectively.Left ventricular ejection fraction (LVEF) increased to (69.1±2.8)% in 8 patients and decreased to(42.8±2.1)% in 11 patients.In the negative group,reversible and irreversible perfusion defects were found in 37 and 13 patients,respectively.LVEF increased to(70.8±4.0)% in 38 patients and decreased to(48.9±2.7)% in 12 patients.The values of ischemic area,severity and extent of perfusion defect,and LVEF were significantly different between the two groups(t=9.28,16.51,2.65;P<0.001,<0.001,<0.01,respectively).Conclusions Gated ~(99)Tc~m-MIBI myocardial perfusion imaging is valuable in assessing patients with hypertrophic cardiomyopathy.Detection for the presence or absence of coexisting coronary artery disease and myocardial ischemia has an important prognostic indication and management indication for these patients.
8.Role of hepatic H19 expression in glucose metabolism disorder inducedby p,p'-dichlorodiphenyldichloroethylene
Xiaochen GUO ; Ming GAO ; Xueyun PENG ; Nanxiang WU
Journal of Preventive Medicine 2022;34(7):659-664
Objective :
To investigate the role of hepatic long-chain non-coding RNA (lncRNA) H19 in key genes associated with glucose metabolism disorder induced by p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE).
Methods:
Human embryonic liver CCC-HEL-1 cells were divided into the DMSO group, 0.1 μmol/L p,p′-DDE group, 1 μmol/L p,p′-DDE group, 10 μmol/L p,p′-DDE group, small interference RNA (siRNA)+DMSO group and siRNA+10 μmol/L p,p′-DDE group. The promoter region methylation, mRNA expression and protein expression of hepatocyte nuclear factor 4α (HNF4α), forkhead box transcription factor O1 (FoxO1) and insulin-like growth factor (IGF2) were detected in CCC-HEL-1 cells using the bisulfite method, real-time fluorescence quantitative PCR (qPCR) assay and BCA assay, respectively. The changes in H19 mRNA expression, the methylation of associated genes in the promoter region and transcriptional expression were compared in CCC-HEL-1 among groups.
Results:
Exposure to p,p′-DDE alone at different doses resulted in an increase in H19 expression, and the H19 mRNA expression was higher in the 10 μmol/L p,p′-DDE group than in the DMSO group [(1.31±0.25) vs. (1.02±0.22); P<0.05]. Lower methylation of the HNF4α gene in the pro moter region [(38.59±32.77)% vs. (61.43±24.64)%; P<0.05] and higher HNF4α mRNA expression [(1.33±0.26) vs. (1.03±0.28); P<0.05] were detected in the 10 μmol/L p,p′-DDE group than in the DMSO group, while no significant differences were detected between the two groups in terms of the methylation of FoxO1 and IGF2 genes in the promoter region, FoxO1 and IGF2 mRNA and protein expression (P>0.05). Following siRNA-induced H19 knockdown, higher methylation of the HNF4α gene in the promoter region [(71.33±22.23)% vs. (38.59±32.78)%; P<0.05], lower HNF4α mRNA expression [(0.71±0.17) vs. (1.33±0.26); P<0.05], higher methylation of FoxO1 gene in the promoter region [(47.73±34.24)% vs. (25.09±25.35)%; P<0.05] and higher IGF2 mRNA [(1.39±0.25) vs. (0.80±0.20); P<0.05] were found in the siRNA+DMSO group than in the 10 μmol/L p,p′-DDE group, and higher IGF2 protein expression was detected in the siRNA+DMSO group than in the DMSO group [(1.03±0.11) vs. (0.74±0.12); P<0.05].
Conclusion
Hepatic H19 may alter HNF4α, FoxO1 and IGF2 transcription and expression through mediating the methylation of genes in the promoter region, thereby playing a role in p,p′-DDE-induced glucose metabolism disorders.
9.Temperature Sensation Threshold of Trunk Skin in Healthy Adults
Hui-li ZHANG ; Ming-ming GAO ; Hua-zhen GUO ; Gui-yun SONG ; Pu ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2015;21(7):804-806
Objective To measure the temperature sensation threshold of trunk skin in healthy adults. Methods The threshold of cold sensation, warm sensation, cold pain sensation and heat pain sensation of trunk skin key points (T3, T7 and T11) were measured with Thermal Sensory Analyzer in 123 healthy adults. Results The thresholds of cold, warm, cold pain and heat pain sensations were obtained. The standard deviation of cold and warm threshold was less than that of heat pain. The range of cold sensation threshold was the largest. The heat pain sensation threshold increased with segmental declining and the sensation threshold increased with age. Conclusion Normal reference value should be established variously with the segment and age. The threshold of cold, warm varies less, while the threshold of cold pain and heat pain varies too much.